Biomarker Approach to Screening for the early detection of HPV-related Oropharyngeal Cancer (BASH OPC)

早期检测 HPV 相关口咽癌的生物标志物筛查方法 (BASH OPC)

• 批准号: 10769204
• 负责人: Antonio Luigi Amelio
• 金额: $ 72.71万
• 依托单位: H. LEE MOFFITT CANCER CTR & RES INST
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-04 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10769204
• 关键词: Address; Age; Awareness; Biological Assay; Biological Markers; Biological Specimen Banks; Breast Cancer Detection; Cancer Burden; Cancer Center; Cancer Detection; Cancer Patient; Cervical Cancer Screening; Clinical; Collaborations; DNA; Data; Dental General Practice; Detection; Development; Diagnosis; Disease; Early Detection Research Network; Early Diagnosis; Epidemiologist; Epidemiology; Epigenetic Process; Ethnic Origin; Evaluation; Follow-Up Studies; Genes; Goals; HPV oropharyngeal cancer; Human Papilloma Virus Vaccination; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; Incidence; Individual; Infrastructure; Ipsilateral; Laboratories; Lesion; Literature; Malignant Neoplasms; Measures; Medical; Medical Oncologist; Medical center; Methods; Methylation; Modality; Morbidity - disease rate; Mouth Neoplasms; Oral; Oral health; Oropharyngeal; Patient-Focused Outcomes; Performance; Phase; Positive Lymph Node; Prevention; Prevention approach; Primary Prevention; Race; Radiation Oncologist; Research; Research Infrastructure; Resources; Sampling; Screening for cancer; Secondary Prevention; Sensitivity and Specificity; Series; Site; Specimen; Tobacco; Tobacco use; Tumor Tissue; Tumor-Derived; Universities; Validation; Viral; biobank; biomarker development; biomarker panel; cancer diagnosis; case control; chemoradiation; clinical assay development; colorectal cancer screening; data repository; design; disability; early screening; experience; genome wide methylation; high risk population; improved; improved outcome; innovation; malignant oropharynx neoplasm; men; mortality; neoplastic; noninvasive diagnosis; oral HPV; prospective; screening; sex; success; tumor

ABSTRACT Oropharyngeal cancer (OPC) incidence is significantly increasing with most cases (~80%) caused by human papillomavirus (HPV) infection type 16. The majority of OPC cases are diagnosed late and require intensive chemo-radiation causing significant morbidity, life-long disabilities, and mortality. Early OPC detection is currently the most viable secondary prevention approach with the potential to vastly improve outcomes for OPC patients. We completed a series of studies focused on developing an oral gargle biomarker panel suitable for early OPC detection that can be measured in a single oral gargle specimen, and can discriminate between early OPC (T1- 2 N0-1 [small tumors with a single ipsilateral node ≤3 cm]) cases and controls in two different case-control sets. In a follow-up study the biomarker panel specificity and sensitivity was improved (AUC = 0.935) with a genome- wide methylation array discovery approach. This resulted in panel expansion to include oral HPV 16 status and 13 differentially methylated host gene CpG sites. We are now poised to advance this oral gargle biomarker panel to the second phase of biomarker development. We propose to leverage existing biorepositories of early OPC cases and research infrastructure at two cancer centers to efficiently advance clinical assay development and validation. Our goal is to validate a non-invasive diagnostic biomarker panel to detect OPC early. The central hypothesis is that we can distinguish early OPC cases from cancer-free individuals using biomarkers related to HPV and host epigenetic alterations, thereby identifying tumors that can be effectively and safely treated with a single modality where survival is highest. As we are keenly aware that this is an evolving field, we will also conduct preliminary evaluation of these and other biomarkers as the literature evolves. The Primary Aim is to estimate the sensitivity and specificity of a combined HPV 16 DNA and host gene methylation oral biomarker panel to distinguish early OPC cases from controls among 100 early and 100 late disease pre-treatment OPC cases, and 200 controls matched by sex, age, race, and tobacco from the Moffitt Cancer Center and the UPMC Hillman Cancer Center. Secondary Aims include assessing inter- and within-laboratory biomarker concordance and reliability, factors associated with the biomarker panel separately among cases and controls, and the performance of other differentially methylated host genes (e.g., SYNGR3) and/or oral tumor-tissue modified HPV DNA to detect OPC early. This is an innovative approach to OPC early detection, using a non-invasive specimen readily obtained (e.g., in routine dental practice). The approach builds on existing clinical/epidemiologic infrastructure, well annotated biorepository and data from OPC cases and controls, and strong preliminary data. Our research team has the experience and expertise to successfully implement the proposed study. Results will inform the design of a large definitive prospective screening trial of a biomarker panel measured in a non-invasive specimen among high-risk individuals to shift OPC diagnosis from late to early disease.

抽象的 大多数情况下，口咽癌（OPC）的发病率显着增加（约80％） 乳头瘤病毒（HPV）感染16型。大多数OPC病例被诊断出来，需要密集 化学辐射导致明显的发病率，终身残疾和死亡率。目前正在使用早期OPC检测 最可行的二级预防方法，有可能大大改善OPC患者的预后。 我们完成了一系列研究，重点是开发适合早期OPC的口服gargle生物标志物面板 可以在单个口腔垃圾标本中测量的检测，可以区分早期OPC（T1- 2 N0-1 [单一同侧节点≤3cm]）病例和对照组中的对照组中的对照组。 在一项随访研究中，生物标志物面板的特异性和灵敏度得到了提高（AUC = 0.935），具有基因组 - 宽甲基化阵列发现方法。这导致面板扩展包括口服HPV 16状态和 13种不同的甲基化宿主基因CpG位点。现在，我们被毒死了这个口头gargle生物标志物面板 到生物标志物开发的第二阶段。我们建议利用早期OPC的现有生物库 两个癌症中心的病例和研究基础设施，以有效提高临床评估发展和 验证。我们的目标是验证非侵入性诊断生物标志物面板以尽早检测OPC。中央 假设是我们可以使用与 HPV和宿主的表观遗传改变，从而鉴定可以有效，可以安全地处理的肿瘤 生存最高的单一模态。正如我们敏锐地意识到这是一个不断发展的领域，我们也将 对这些和其他生物标志物进行初步评估，作为文献的发展。主要目的是 估计组合HPV 16 DNA和宿主基因甲基化口服生物标志物的敏感性和特异性 面板以区分早期OPC病例与100个早期和100个晚期疾病预处理的对照OPC 案件和200个控制与莫菲特癌症中心和UPMC的性别，年龄，种族和烟草相匹配 希尔曼癌症中心。次要目的包括评估间和实验室内生物标志物的一致性 以及可靠性，与生物标志物面板相关的因素，分别在病例和对照组之间 其他不同甲基化的宿主基因（例如Syngr3）和/或口服肿瘤修饰的HPV的性能 DNA早期检测OPC。这是使用非侵入性标本的OPC早期检测的创新方法 很容易获得（例如，在常规牙科实践中）。该方法以现有的临床/流行病学为基础 来自OPC病例和对照的基础架构，注释良好的生物座和数据以及强大的初步数据。 我们的研究团队具有成功实施拟议研究的经验和专业知识。结果将 告知在非侵入性测量的生物标记面板的大型确定性前瞻性筛查试验的设计 高风险个体中的标本将OPC诊断从晚期转变为早期疾病。